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Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

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      Abstract

      The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

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      In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.
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        Dissociable intrinsic connectivity networks for salience processing and executive control.

        Variations in neural circuitry, inherited or acquired, may underlie important individual differences in thought, feeling, and action patterns. Here, we used task-free connectivity analyses to isolate and characterize two distinct networks typically coactivated during functional MRI tasks. We identified a "salience network," anchored by dorsal anterior cingulate (dACC) and orbital frontoinsular cortices with robust connectivity to subcortical and limbic structures, and an "executive-control network" that links dorsolateral frontal and parietal neocortices. These intrinsic connectivity networks showed dissociable correlations with functions measured outside the scanner. Prescan anxiety ratings correlated with intrinsic functional connectivity of the dACC node of the salience network, but with no region in the executive-control network, whereas executive task performance correlated with lateral parietal nodes of the executive-control network, but with no region in the salience network. Our findings suggest that task-free analysis of intrinsic connectivity networks may help elucidate the neural architectures that support fundamental aspects of human behavior.
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          Experimental and theoretical approaches to conscious processing.

          Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network. We compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Author and article information

            Affiliations
            [1 ]Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen, Denmark
            [2 ]Cyclotron Research Centre and Neurology Department, University and University Hospital of Liège , Liège, Belgium
            [3 ]Department of Nuclear Medicine and PET Centre, Aarhus University Hospital , Aarhus, Denmark
            [4 ]Centre for Advanced Imaging, University of Queensland , Brisbane, Australia
            [5 ]Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, Massachusetts, USA
            [6 ]Department of Biomedicine—Pharmacology, Aarhus University , Aarhus, Denmark
            [7 ]Department of Nuclear Medicine, University Hospital of Liège , Liège, Belgium
            [8 ]Department of Neurology, McGill University , Montréal, Québec, Canada
            [9 ]Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland, USA
            Author notes
            [* ]Department of Neuroscience and Pharmacology, Panum Institute , Blegdamsvej 3, Copenhagen N 220, Denmark. E-mail: Gjedde@ 123456sund.ku.dk
            [10]

            These authors contributed equally to the work.

            Journal
            J Cereb Blood Flow Metab
            J. Cereb. Blood Flow Metab
            Journal of Cerebral Blood Flow & Metabolism
            Nature Publishing Group
            0271-678X
            1559-7016
            January 2015
            08 October 2014
            1 January 2015
            : 35
            : 1
            : 58-65
            25294128
            4294395
            jcbfm2014169
            10.1038/jcbfm.2014.169
            Copyright © 2015 International Society for Cerebral Blood Flow & Metabolism, Inc.

            This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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